1. HPERTHYROIDISM MANAGMENT

3. RECOMMENDATION 2 Beta-adrenergic blockade should be given to elderly patients with symptomatic thyrotoxicosis and to other thyrotoxic patients with resting heart rates in excess of 90 bpm or coexistent cardiovascular disease.

4. RECOMMENDATION 3 Beta-adrenergic blockade should be considered in all patients with symptomatic thyrotoxicosis.

5. RECOMMENDATION 4 Patients with overt Graves’ hyperthyroidism should be treated with any of the following modalities: 131I therapy, antithyroid medication, or thyroidectomy.

6. Factors that favor a particular modality as treatment for Graves’ hyperthyroidism :

7. 131I: Females planning a pregnancy in the future (in more than 4–6 months following radioiodine therapy, provided thyroid hormone levels are normal), individuals with comorbidities increasing surgical risk, and patients with previously operated or externally irradiated necks, or lack of access to a high-volume thyroid surgeon or contraindications to ATD use.

8. ATDs: Patients with high likelihood of remission (patients, especially females, with mild disease, small goiters, and negative or low-titer TRAb); the elderly or others with comorbidities increasing surgical risk or with limited life expectancy;

9. individuals in nursing homes or other care facilities who may have limited longevity and are unable to follow radiation safety regulations; patients with previously operated or irradiated necks; patients with lack of access to a high- volume thyroid surgeon; and patients with moderate to severe active GO..

10. Surgery: Symptomatic compression or large goiters (≥80 g); relatively low uptake of radioactive iodine; when thyroid malignancy is documented or suspected (e.g., suspicious or indeterminate cytology); large nonfunctioning, photopenic, or

11. hypofunctioning nodule; coexisting hyperparathyroidism requiring surgery; females planning a pregnancy in <4–6 months (i.e., before thyroid hormone levels would be normal if radioactive iodine were chosen as therapy), especially if TRAb levels are particularly high; and patients with moderate to severe active GO.

13. Contraindications to a particular modality as treatment for Graves’ hyperthyroidism

14. 131I therapy: Definite contraindications include pregnancy, lactation, coexisting thyroid cancer, or suspicion of thyroid cancer, individuals unable to comply with radiation safety guidelines and females planning a pregnancy within 4–6 months.

15. ATDs: Definite contraindications to long- term ATD therapy include previous known major adverse reactions to ATDs.

16. Surgery: Factors that may mitigate against the choice of surgery include substantial comorbidity such as cardiopulmonary disease, end-stage cancer, or other debilitating disorders. Pregnancy is a relative contraindication and should only be used in this circumstance, when rapid control of hyperthyroidism is required and antithyroid medications cannot be used.

17. Thyroidectomy is best avoided in the first and third trimesters of pregnancy because of teratogenic effects associated with anesthetic agents and increased risk of fetal loss in the first trimester and increased risk of preterm labor in the third.

18. Optimally, thyroidectomy is performed in the latter portion of the second trimester. Although it is the safest time, it is not without risk (4.5%–5.5% risk of preterm labor)

19. RECOMMENDATION 5 Patients with GD who are at increased risk for complications due to worsening of hyperthyroidism (i.e., those who are extremely symptomatic or have free T4 estimates 2–3 times the upper limit of normal) should be treated with beta- adrenergic blockade prior to radioactive iodine therapy.

20. RECOMMENDATION 6 Pretreatment with methimazole prior to radioactive iodine therapy for GD should be considered in patients who are at increased risk for complications due to worsening of hyperthyroidism (i.e., those who are extremely symptomatic or have free T4 estimate 2–3 times the upper limit of normal).

21. RECOMMENDATION 7 Medical therapy of any comorbid conditions should be optimized prior to administering radioactive iodine

22. RECOMMENDATION 8 Sufficient radiation should be administered in a single dose (typically 10–15 mCi) to render the patient with GD hypothyroid.

23. RECOMMENDATION 9 A pregnancy test should be obtained within 48 hours prior to treatment in any female with childbearing potential who is to be treated with radioactive iodine. The treating physician should obtain this test and verify a negative result prior to administering radioactive iodine.

24. RECOMMENDATION 10 The physician administering the radioactive iodine should provide written advice concerning radiation safety precautions following treatment. If the precautions cannot be followed, alternative therapy should be selected.

25. RECOMMENDATION 11 Follow-up within the first 1–2 months after radioactive iodine therapy for GD should include an assessment of free T4 and total T3. If the patient remains thyrotoxic, biochemical monitoring should be continued at 4–6 week intervals.

26. RECOMMENDATION 12 When hyperthyroidism due to GD persists after 6 months following 131I therapy, or if there is minimal response 3 months after therapy, retreatment with 131I is suggested.

27. ATDs have been employed for six decades (81). The goal of the therapy is to render the patient euthyroid as quickly and safely as possible. These medications do not cure Graves’ hyperthyroidism. However, when given in adequate doses, they are very effective in controlling the hyperthyroidism;.

28. when they fail to achieve euthyroidism, the usual cause is nonadherence (82). The treatment might have a beneficial immunosuppressive role, but the major effect is to reduce the production of thyroid hormones and maintain a euthyroid state while awaiting a spontaneous remission

29. RECOMMENDATION 13 Methimazole should be used in virtually every patient who chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy when propylthiouracil is preferred, in the treatment of thyroid storm, and in patients with minor reactions to methimazole who refuse radioactive iodine therapy or surgery

30. RECOMMENDATION 14 Patients should be informed of side effects of antithyroid drugs and the necessity of informing the physician promptly if they should develop pruritic rash, jaundice, acolic stools or dark urine, arthralgias, abdominal pain, nausea, fatigue, fever, or pharyngitis.

31. Before starting antithyroid drugs and at each subsequent visit, the patient should be alerted to stop the medication immediately and call their physician when there are symptoms suggestive of agranulocytosis or hepatic injury. ■

33. RECOMMENDATION 15 Prior to initiating antithyroid drug therapy for GD, we suggest that patients have a baseline complete blood count, including white count with differential, and a liver profile including bilirubin and transaminases

34. RECOMMENDATION 16 A differential white blood cell count should be obtained during febrile illness and at the onset of pharyngitis in all patients taking antithyroid medication. Routine monitoring of white blood counts is not recommended.

35. RECOMMENDATION 17 Liver function and hepatocellular integrity should be assessed in patients taking propylthiouracil who experience pruritic rash, jaundice, light-colored stool or dark urine, joint pain, abdominal pain or bloating, anorexia, nausea, or fatigue

36. RECOMMENDATION 18 Minor cutaneous reactions may be managed with concurrent antihistamine therapy without stopping the antithyroid drug. Persistent minor side effects of antithyroid medication should be managed by cessation of the medication 1/+00

37. and changing to radioactive iodine or surgery, or switching to the other antithyroid drug when radioactive iodine or surgery are not options. In the case of a serious allergic reaction, prescribing the alternative drug is not recommended.

38. RECOMMENDATION 19 If methimazole is chosen as the primary therapy for GD, the medication should be continued for approximately 12–18 months, then tapered or discontinued if the TSH is normal at that time.

39. RECOMMENDATION 20 Measurement of TRAb levels prior to stopping antithyroid drug therapy is suggested, as it aids in predicting which patients can be weaned from the medication, with normal levels indicating greater chance for remission.

40. RECOMMENDATION 21 If a patient with GD becomes hyperthyroid after completing a course of methimazole, consideration should be given to treatment with radioactive iodine or thyroidectomy. Low-dose methimazole treatment for longer than 12–18 months may be considered in patients not in remission who prefer this approach.

41. RECOMMENDATION 22 Whenever possible, patients with GD undergoing thyroidectomy should be rendered euthyroid with methimazole. Potassium iodide should be given in the immediate preoperative period.

42. RECOMMENDATION 23 In exceptional circumstances, when it is not possible to render a patient with GD euthyroid prior to thyroidectomy, the need for thyroidectomy is urgent, or when the patient is allergic to antithyroid medication,

43. the patient should be adequately treated with beta-blockade and potassium iodide in the immediate preoperative period. The surgeon and anesthesiologist should have experience in this situation.

44. RECOMMENDATION 24 If surgery is chosen as the primary therapy for GD, near-total or total thyroidectomy is the procedure of choice.

46. RECOMMENDATION 25 If surgery is chosen as the primary therapy for GD, the patient should be referred to a high-volume thyroid surgeon

47. RECOMMENDATION 26 Following thyroidectomy for GD, we suggest that serum calcium or intact parathyroid hormone levels be measured, and that oral calcium and calcitriol supplementation be administered based on these result

48. RECOMMENDATION 27 Antithyroid drugs should be stopped at the time of thyroidectomy for GD, and beta-adrenergic blockers should be weaned following surgery.

49. RECOMMENDATION 28 Following thyroidectomy for GD, L- thyroxine should be started at a daily dose appropriate for the patient’s weight (0.8 μg/lb or 1.7 μg/kg), and serum TSH measured 6–8 weeks postoperatively.

50. RECOMMENDATION 29 If a thyroid nodule is discovered in a patient with GD, the nodule should be evaluated and managed according to recently published guidelines regarding thyroid nodules in euthyroid individuals.

51. RECOMMENDATION 30 A multimodality treatment approach to patients with thyroid storm should be used, including beta-adrenergic blockade, antithyroid drug therapy, inorganic iodide, corticosteroid therapy, aggressive cooling with acetaminophen and cooling blankets, volume resuscitation, respiratory support and monitoring in an intensive care unit.

53. ■ RECOMMENDATION 50 Children with GD should be treated with methimazole, 131I therapy, or thyroidectomy. 131I therapy should be avoided in very young children (<5 years). 131I therapy in patients between 5 and 10 years of age is..

54. RECOMMENDATION 51 Methimazole should be used in virtually every child who is treated with antithyroid drug therapy.

55. RECOMMENDATION 59 Pediatric patients with GD who are not in remission following 1–2 years of methimazole therapy should be considered for treatment with radioactive iodine or thyroidectomy.

56. RECOMMENDATION 60 We suggest that children with GD having total T4 levels of >20 ug/dL (260 nmol/L) or free T4 estimates >5 ng/dL (60 pmol/L) who are to receive radioactive iodine therapy be pretreated with methimazole and beta-adrenergic blockade until total T4 and/or free T4 estimates normalize before proceeding with radioactive iodine.

57. RECOMMENDATION 61 If 131I therapy is chosen as treatment for GD in children, sufficient 131I should be administered in a single dose to render the patient hypothyroid.

59. SUBCLINICAL HYPERTHYROIDISM

60. 2 / 98medslides.com60 Subclinical Hyperthyroidism Definition: –Low TSH TSH level <0.1 mU/L (0.4-5.0 mU/L) –Normal thyroxine (T4) free T4 level (0.7-1.8 ng/dl) or free T4 index (6.4-10.7 ug/dl) –Normal triiodothyronine (T3) T3 level (94-170 ng/dl) Clev Clinic J Med 1998; 68:65-66

61. SH has a prevalence of about 1% in the general population (245). In older persons, TMNG is probably the most common cause of SH, with other etiologies of endogenous SH, including GD, solitary autonomously functioning nodules, and various forms of thyroiditis (246,247), the latter of which would be more strictly termed “subclinical thyrotoxicosis

62. Some otherwise healthy older persons may have low serum TSH levels, low normal serum levels of free T4 estimates and T3, and no evidence of thyroid or pituitary disease, suggesting an altered set point of the pituitary-thyroid axis (

63. 2 / 98medslides.com63 Significance of Low TSH Low serum TSH may be transient In a British study (1) 66 elderly patients with abnormal TSH 61% had normal TSH 1 year later In a Swedish study (2) 53 euthyroid patient with low TSH 53% had normal value 2-3 wks later 1. Clin Endocrinology 1991; 34:77-83 2. Br Med J 1988; 297:1586-1592

64. 2 / 98medslides.com64 Subclinical Hyperthyroidism consequences Cardiac effects –atrial fibrillation (AF), frequent premature atrial contractions, sinus tachycardia –risk of AF is 3x higher if TSH is  0.1 mU/L (1) –increased ventricular mass & contractility Accelerated bone loss –especially in women not receiving estrogen replacement therapy (2) 1. N Eng J Med 1994; 331:1249-1252 2. JAMA 1994; 271:124-1249

66. This situation can mimic SH biochemically, and it may be difficult to rule out clinically, although scintigraphic studies suggesting autonomous thyroid function would favor SH. Other causes of a suppressed TSH but normal estimated free T4 and T3 include corticosteroid therapy, central hypothyroidism, and nonthyroidal illness

67. RECOMMENDATION 66 When TSH is persistently below the lower limit of normal but ≥0.1 mU/L, treatment of SH should be considered in individuals ≥65 years of age and in patients with cardiac disease or symptoms of hyperthyroidism. 2/+00

68. RECOMMENDATION 67 If SH is to be treated, the treatment should be based on the etiology of the thyroid dysfunction and follow the same principles as outlined for the treatment of overt hyperthyroidism.

70. Graves' disease  Graves' disease is the most common thyroid abnormality associated with thyroid orbitopathy, but other disorders of the thyroid can have similar ocular manifestations. These include Hashimoto's thyroiditis, thyroid carcinoma, primary hyperthyroidism, and neck irradiation.

71. .. Approximately 40% of patients with Graves' disease have or will develop thyroid orbitopathy.

72. Both hyperthyroid and euthyroid patients can develop clinical signs and symptoms of thyroid orbitopathy. In general, patients with euthyroid Graves' disease tend to have less severe orbitopathy

73. THYROID EYE DISEASE  LID RETRACTION1. sympathetic overactivity infiltration of levator / SR complex. hypotropia (retraction disappears on downgaze)  SIGNS:- Dalrymples (lid retraction), von Graefe (lid lag), Kocher´s (staring appearance)

74. THYROID EYE DISEASE  INFILTRATION  1. soft tissue involvement :- chemosis, conjunctival injection over the recti insertions, puffy lids

75. THYROID EYE DISEASE  Superior limbic keratoconjunctivitis (SLK)

76. INVESTIGATION RADIOLOGICAL TESTSOrbital CT (enlarged muscle belly, tendon normal). Coca-Cola bottle sign = muscle swelling deforming ethmoidal bones.MRI T2 showing oedema of muscles; repeating the scan in different positions of gaze can create a pseudo- video of eye movements (for assessment of muscle restriction).

77. TREATMENT Acute Congestive Orbitopathy  1. SYMPTOMATIC:- elevate bedhead, lubricants, lid taping, diuretics  2. SYSTEMIC:-  a) Normalise thyroid function with or without thyroxine.  Patients rendered euthyroid do improve their GO score  Tallstedt trial N Eng J Med 1992 antithyroid drugs cause a 10% chance of new or worsening GO but radio-iodine causes a 30% chance of new or worsening GO.

78. TREATMENT Acute Congestive Orbitopathy  Corticosteroids have been used successfully in the treatment of acute coSteroid Therapyngestive orbitopathy Radiation therapy Orbital decompression

80. Corticosteroids have been used successfully in the treatment of acute congestive orbitopathy  Corticosteroids have been used successfully in the treatment of acute congestive orbitopathy. They are believed to work by altering cell-mediated immune response and diminishing the production of mucopolysaccharides by the orbital fibroblasts.Corticosteroids result in improvement of soft tissue involvement and compressive optic neuropathy (but do not have as much of an effect on diplopia Traditionally, a "short burst" of high-dose corticosteroids has been given, usually in the range of 60 to 120 mg/day of oral prednisone. Improvement in subjective symptoms such as pain and tearing usually occurs first, often as early as 24 to 48 hours, followed by improvement in soft tissue congestion and muscle function over a period of days to weeks.

81. Steroid Therapy  Prednisone or prednisolone  This is standard treatment but there are frequent side effects. No response in 35% of patients and anyway the response is only partial. High dose steroids given early in the disease when muscle swelling occurs does not necessarily limit the long term course of the disease. If there is no response to high dose steroids in the first three weeks they should be rapidly reduced. Prednisolone + orbital radiotherapy has slightly more effect than either alone.Use high dose pulsed methylprednisolone if urgent optic nerve decompression is required, This is more effective than oral treatment but it is expensive and not justified in most cases of TED.

82. Radiation therapy  During the past few years, radiation therapy has reemerged as a useful form of treatment of severe orbitopathy. The rationale for the use of radiation therapy is reduction or elimination of the pathogenic orbital lymphocytes, which are markedly radiosensitive. It is also thought that the glycosaminoglycan production by fibroblasts is reduced, thereby reducing orbital edema, orbital tension, and conjunctival injection. Although congestive findings improve most consistently, significant improvement in proptosis and extraocular muscle function has been reported.Like corticosteroids, radiation therapy is most effective within the first year, when significant fibrotic changes have not yet occurred. Mourits and associates,135 however, suggest that periods of active orbital inflammation within the long natural history of thyroid orbitopathy would benefit from corticosteroids or radiation therapy.

83. Radiotherapy  RETROBULBAR RADIOTHERAPY:- Trial of prednisone versus radiotherapy showed no difference in clinical improvement (about 50%).The patients all tolerated retrobulbar radiotherapy better than steroids Consider if steroid maintenance > 25mg/ day. Best effect in acute disease.Do not irradiate patients with diabetes mellitus as they are more susceptible to radiation retinopathy.2000rads/ 10days, effect starts at 4 weeks, maximal 4 months.

84. Compressive Optic Neuropathy  Compressive optic neuropathy can cause permanent visual loss. The treatment possibilities include high doses of corticosteroids, irradiation, and orbital decompression. Some patients require only one of these modalities, while other patients need combined therapies.

85. Compressive Optic Neuropathy  As in the treatment of acute congestive thyroid orbitopathy, radiation therapy is becoming increasingly popular. A retrospective series of 84 patients with compressive optic neuropathy treated with either corticosteroids or radiation therapy supports mounting evidence that radiation therapy may be safer and more effective than corticosteroids.  Radiation therapy, however, must be administered in fractionated doses, which delays its beneficial effect. For this reason, if visual dysfunction progresses while the patient is on corticosteroids, surgical decompression is usually recommended if the patient is a surgical candidate.

86. Orbital decompression  Orbital decompression is indicated for compressive optic neuropathy when there has been failure of or contraindication for corticosteroids or radiation therapy or if corticosteroid dependence has developed with intolerable side effects. Other indications include excessive proptosis with exposure keratitis and corneal ulceration, pain relief, and cosmesis for disfiguring exophthalmos. Orbital decompression may also be indicated as a preliminary procedure to extraocular muscle surgery on a patient with sufficient proptosis to suggest that decompression might ultimately be required.

87. Orbital decompression  A variety of approaches may be used, each with its own advantages and associated complications.  The transorbital (via fornix or eyelid) approach to inferior and medial wall decompression is the most common approach used by ophthalmologists. The addition of a lateral wall advancement has the advantage of both further increasing the orbital volume and simultaneously improving upper eyelid retraction; this is the technique we prefer.

88. ORBITAL DECOMPRESSION  Subciliary approach.Inferior & medial wall (6mm proptosis).Remove bone to posterior wall maxillary sinus (5mm more posterior on medial wall), Avoid IO neurovascular bundle, and the anterior and posterior ethmoidal arteries.Incise periosteum in A-P direction posteriorly and circumferentially anteriorly.  Complications:  visual loss,  A pattern ET

89. Motility Disorders  A major source of morbidity in thyroid orbitopathy, and the most frequent problem associated with orbital decompression surgery, has been strabismus. In patients with relatively minimal degrees of ocular misalignment, diplopia can be avoided with a compensatory head posture, Fresnel plastic press-on prisms, or temporary occlusion. Unfortunately there is significant image degradation as larger prisms are used, limiting their efficacy. If there is marked asymmetry in ocular deviation in different fields of gaze, prisms are also less effective. In some cases during the inflammatory period, use of intramuscular botulinum toxin has shown some efficacy.  Extraocular muscle surgery should be postponed until the muscles are no longer inflamed and the deviation has remained stable for at least 6 months.

90. Surgery  STRABISMUS SURGERY:-Aim for maximal area of fusion without abnormal head posture.IR recession on adjustable +/- contra SR recession iii) EYELID SURGERY:-  Upper Lid retraction - Muller´s tenotomy (<2mm), levator Z myotomy or recession on hangback sutures, levator tenotomy +/- horns.  Lower Lid retraction - Usually needs a spacer from donor sclera (lid retraction X 2 = amount of sclera required)  iv) BLEPHAROPLASTY for excess skin and fat  Ideally treatment combines a multidisciplinary coherent approach such as  Combined radiotherapy and immunosuppression trial

91. Eyelid Abnormalities  As with other thyroid eye problems, eyelid retraction will often improve with time, and only an estimated 50% of patients with eyelid retraction have a significant eyelid abnormality 5 years later.  Eyelid retraction can result from excessive autonomic discharge, levator fibrosis, or contraction of the inferior rectus muscle.  Surgical correction of eyelid abnormalities should be performed only after orbital or extraocular muscle surgery because these operations may change eyelid position. For example, inferior rectus muscle restriction may cause upper eyelid retraction because of the superior rectus/levator palpebrae superioris overaction against the restriction. Specific techniques for repair of eyelid retraction are discussed in other chapters.

92. THYROID EYE DISEASE  The goal is to identify and treat patients who are at particular risk of sight threatening complications. The disease has a finite period of activity until it becomes burnt out.The yellow region shows the early phase where there is the best response to treatment.  Type 1 younger age group, whiter eyes with proptosis. Inflammation is mostly in orbital fat not muscles.  Type 11 older patient with red eyes, severe sight threatening disease, tobacco addiction is frequent.

93.  (orbitopathy in general is worst in the older age groups.)   LID RETRACTION1. sympathetic overactivity2. infiltration of levator / SR complex3. hypotropia (retraction disappears on downgaze)  SIGNS:- Dalrymples (lid retraction), von Graefe (lid lag), Kocher´s (staring appearance) 

94.  INFILTRATION  1. soft tissue involvement :- chemosis, conjunctival injection over the recti insertions, puffy lids 

95.  Superior limbic keratoconjunctivitis (SLK) due to redundant conjunctiva   2. muscle involvement :- diplopia due to restriction.  Order of involvement IR, MR, SR (LR)  Braley´s sign = increased IOP on upgaze (>4mmHg)   3. proptosis :- TED is the commonest cause of unilateral or bilateral proptosis 

96.  (orbitopathy in general is worst in the older age groups.)   LID RETRACTION1. sympathetic overactivity2. infiltration of levator / SR complex3. hypotropia (retraction disappears on downgaze)  SIGNS:- Dalrymples (lid retraction), von Graefe (lid lag), Kocher´s (staring appearance)   INFILTRATION  1. soft tissue involvement :- chemosis, conjunctival injection over the recti insertions, puffy lids 

97. VISUAL FIELD  A visual field should be performed in all patients suspected to have optic neuropathy and is useful when following patients after initiation of treatment. Characteristically, a central scotoma or an inferior altitudinal defect is seen in cases of compressive optic neuropathy. Other visual field defects include an enlarged blind spot, paracentral scotoma, nerve fiber bundle defect, or generalized constriction.

98. ULTRASONOGRAPHY  Ultrasonography can be useful to detect early thyroid disease in patients with equivocal laboratory tests. Most patients with Graves' disease, even those without overt eye findings, have ultrasonographic evidence of extraocular muscle involvement.46 Ultrasonography is believed by some to be more accurate than CT in detecting enlargement of the extraocular muscles. Also, visualization of the tendinous insertions onto the globe may be more accurately assessed using ultrasonography when differentiating enlarged extraocular muscles secondary to myositis from hyperthyroid orbitopathy. Ultrasonography is, however, less suited than CT to assessing muscle thickness at the orbital apex.  This test may also be helpful in distinguishing between active and inactive disease. Examination of the extraocular muscles shows that there is a lower internal reflectivity in active as compared with inactive disease.

99. CT findings in thyroid orbitopathy  The most characteristic CT finding in thyroid orbitopathy is enlargement of the extraocular muscles with normal tendinous insertions onto the globe. Other findings include proptosis and anterior prolapse of the orbital septum due to excessive orbital fat and muscle swelling (see Fig. 4).Patients at risk for developing optic neuropathy may also have severe apical crowding, a dilated superior ophthalmic vein, and anterior displacement of the lacrimal gland. Of these, apical crowding is the most sensitive indicator for the presence of optic neuropathy The CT scan should be done in the coronal plane to assess the enlargement of the extraocular muscles at the apex because axial sections can sometimes be misleading.

100. MAGNETIC RESONANCE IMAGING  …… SYSTEMIC THYROID DISEASE

101. Optic neuropathy  Although a history of decreased vision should be carefully sought, it is important to realize that optic neuropathy can occur in a significant number (18%) of patients with visual acuities in the range of 20/20 to 20/25 (6/6 to 6/7.5).*An afferent pupillary defect is present in 35%. An abnormal disc (either swollen or pale) is seen in only 52%. Visual field defects are present in 66%.Other tests that can be useful include color vision testing and visual evoked potentials (VEPs). The Farnsworth-Munsell 100-hue test is a sensitive indicator of optic nerve dysfunction, but pseudoisochromatic screening procedures (e.g.,Ishihara plates) rarely identify an acquired color defect unless optic neuropathy is severe.The pattern reversal VEP is very sensitive at detecting early optic neuropathy and may be a useful means of following patients after treatment.

102. Intraocular pressure  The increased intraocular pressure measured during upgaze in patients with thyroid orbitopathy has been a controversial finding. When restriction of the inferior rectus muscle occurs, the intraocular pressure may increase by 6 mm Hg or more in upgaze as compared with primary gaze. The increased intraocular pressure in upgaze is a normal phenomenon exaggerated by thyroid orbitopathy  In patients with severe infiltrative disease there is an increased pressure on upgaze as compared with normal controls and patients with mild disease. It is often not an indicator of early disease because it occurs infrequently in patients with minimal eye findings

103. INVESTIGATION  SEROLOGICALT3 (hyperthyroid)T4 TSH (hypothyroid)TSI (thyroid stimulating immunoglobulin).  RADIOLOGICAL TESTSOrbital CT (enlarged muscle belly, tendon normal). Coca-Cola bottle sign = muscle swelling deforming ethmoidal bones.MRI T2 showing oedema of muscles; repeating the scan in different positions of gaze can create a pseudo-video of eye movements (for assessment of muscle restriction).  RADIOISOTOPE TESTS Octreoscan: quantitative uptake of radio-labelled octreotide (which is a somatostatin analogue).

104. VISUAL FIELD  A visual field should be performed in all patients suspected to have optic neuropathy and is useful when following patients after initiation of treatment. Characteristically, a central scotoma or an inferior altitudinal defect is seen in cases of compressive optic neuropathy. Other visual field defects include an enlarged blind spot, paracentral scotoma, nerve fiber bundle defect, or generalized constriction.

105. ULTRASONOGRAPHY  Ultrasonography can be useful to detect early thyroid disease in patients with equivocal laboratory tests. Most patients with Graves' disease, even those without overt eye findings, have ultrasonographic evidence of extraocular muscle involvement.46 Ultrasonography is believed by some to be more accurate than CT in detecting enlargement of the extraocular muscles. Also, visualization of the tendinous insertions onto the globe may be more accurately assessed using ultrasonography when differentiating enlarged extraocular muscles secondary to myositis from hyperthyroid orbitopathy. Ultrasonography is, however, less suited than CT to assessing muscle thickness at the orbital apex.  This test may also be helpful in distinguishing between active and inactive disease. Examination of the extraocular muscles shows that there is a lower internal reflectivity in active as compared with inactive disease.

106. INVESTIGATION  SEROLOGICALT3 (hyperthyroid)T4 TSH (hypothyroid)TSI (thyroid stimulating immunoglobulin).  RADIOLOGICAL TESTSOrbital CT (enlarged muscle belly, tendon normal). Coca-Cola bottle sign = muscle swelling deforming ethmoidal bones.MRI T2 showing oedema of muscles; repeating the scan in different positions of gaze can create a pseudo-video of eye movements (for assessment of muscle restriction).  RADIOISOTOPE TESTS Octreoscan: quantitative uptake of radio-labelled octreotide (which is a somatostatin analogue).

107. Optic neuropathy with visual loss  The prevalence of optic neuropathy with visual loss in patients with thyroid orbitopathy is less than 5%.  Optic neuropathy is, however, the most common cause of blindness secondary to thyroid orbitopathy. Its onset is often insidious and may be masked by other symptoms. These patients are usually older (age 50 to 70) are more frequently male, have a later onset of thyroid disease, and more often have diabetes.  Optic neuropathy is usually bilateral, but up to one third of cases may be unilateral.

108. CT findings in thyroid orbitopathy  The most characteristic CT finding in thyroid orbitopathy is enlargement of the extraocular muscles with normal tendinous insertions onto the globe. Other findings include proptosis and anterior prolapse of the orbital septum due to excessive orbital fat and muscle swelling (see Fig. 4).Patients at risk for developing optic neuropathy may also have severe apical crowding, a dilated superior ophthalmic vein, and anterior displacement of the lacrimal gland. Of these, apical crowding is the most sensitive indicator for the presence of optic neuropathy The CT scan should be done in the coronal plane to assess the enlargement of the extraocular muscles at the apex because axial sections can sometimes be misleading.

109. THYROID EYE DISEASE  Orbital CT - (enlarged muscle belly, tendon normal)

110. MAGNETIC RESONANCE IMAGING  MRI using 1.5 tesla units and orbital surface coils provides optimal spatial resolution of the orbit.34 MRI may also be useful in distinguishing between active and inactive disease. The changing intensities between T1- and T2-weighted images may differentiate the active edematous from the inactive fibrotic muscle changes.  Extraocular muscles that have acute inflammation have longer T2 times owing to the higher water content. Because acute inflammatory disease responds better to radiation therapy than chronic fibrosis, the information gained from MRI may theoretically be helpful in choosing patients for radiation therapy.

111. SYSTEMIC THYROID DISEASE  There are no good recent studies of the natural history of untreated hyperthyroidism, but based on older reports, Wilson56 determined that about one third of patients spontaneously improve, one third remain chronically hyperthyroid, and one third progress to thyroid storm and occasionally death. Because it is not possible to predict which patients will spontaneously improve, treatment of thyroid dysfunction is recommended.

112. Thyrotropin receptor antibodies (TRAb).  antibodies were originally classified into those with stimulatory properties called thyroid-stimulating immunoglobulin or antibody (TSI, TSAb) and those with inhibitory properties called TSH-binding inhibiting immunoglobulin or antibody (TBII, TBIA). Both of these groups are now referred to as thyrotropin receptor antibodies (TRAb).

113. Sight Threatening Complications  optic nerve compression :- <5% affected, due to compression of orbital apex by enlarged EOM. Look for decreased VA, colour vision defects, arcuate or central scotomata, swollen optic disc. Confirmation by orbital CT.  Treatment by medical or surgical decompression.  corneal exposure:- potentially serious:- treat with lubricants, lid taping, tarsorrhaphy, decompression  less common causes of visual loss:- glaucoma, vascular compression

114. Thyroid status-  RADIOLOGICAL TESTSOrbital CT (enlarged muscle belly, tendon normal). Coca-Cola bottle sign = muscle swelling deforming ethmoidal bones.MRI T2 showing oedema of muscles; repeating the scan in different positions of gaze can create a pseudo-video of eye movements (for assessment of muscle restriction).

115. TABLE 12-3 Clinical Assessment of the Patient with Graves’ Ophthalmopathy Activity Measures* Spontaneous retrobulbar pain Pain on attempted up or down gaze Redness of the eyelids Redness of the conjunctiva Swelling of the eyelids Inflammation of the caruncle and/or plica Conjunctival edema

116. Severity Measures Lid aperture: distance between lid margins in millimeters with the patient looking in the primary position, sitting relaxed, and with distant fixation Swelling of the eyelids (absent/equivocal, moderate, severe) Redness of the eyelids (absent/present) Redness of the conjunctivae (absent/present) Conjunctival edema (absent, present) Inflammation of the caruncle or plica (absent, present

117. Exophthalmos: measured in millimeters using the same Hertel exophthalmometer and the same intercanthal distance for an individual patient Subjective diplopia score† Eye muscle involvement (ductions in degrees) Corneal involvement (absent/punctate keratopathy/ulcer)

118. Optic nerve involvement: best-corrected visual acuity, color vision, optic disk, relative afferent pupillary defect (absent/present), plus visual fields if optic nerve compression is suspected

119. *Based on the seven classic features of inflammation in Graves’ ophthalmopathy. The clinical activity score (CAS) is the total number of items present; a CAS  3 indicates active ophthalmopathy

120. † Subjective diplopia score: 0  no diplopia; 1  intermittent (i.e., diplopia in primary position of gaze, when tired, or when first awakening); 2  inconstant (i.e., diplopia at extremes of gaze); 3  constant (i.e., continuous diplopia in primary or reading position

121. TABLE 12-4 Incidence of Major Toxic Reactions to Anti-Thyroid Drugs in Adults Side Effect Frequency (%) Comments Polyarthritis 1-2 — ANCA  vasculitis Rare Mostly PTU Agranulocytosis 0.1-0.5 May be more common with PTU Hepatitis 0.1-0.2 PTU only Cholestasis Rare Methimazole only ANCA , antineutrophil cytoplasmic antibody– positive; PTU, propylthiouracil. Adapted from Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352

122. Other Anti-Thyroid Agents Cholecystographic Agents. In doses of 1 g daily, the iodine-containing cholecystographic contrast agent sodium ipodate (or iopanoate) causes a prompt decrease in serum T4 and serum T3 concentrations in patients with hyperthyroidism.

123. These effects result from both the release of iodine and the ability of the agent to inhibit peripheral T3 production from T4—a combination that can be useful in the seriously ill patient. As with iodine itself, however, withdrawal of the drug carries the risk of an exacerbation. Supplies of this and related agents are no longer available in the United States.

124. Lithium. Lithium carbonate also inhibits thyroid hormone secretion but, unlike iodine, it does not interfere with the accumulation of radioiodine. Lithium, 300 to 450 mg every 8 hours, is employed only to provide temporary control of thyrotoxicosis in patients who are allergic to both thionamide and iodide. This is because the blocking

125. effect is often lost with time. The goal is to maintain a serum lithium concentration of 1 mEq/L.185 Another shortterm use for lithium has been as an adjunct to radioiodine therapy, because the drug slows the release of iodine from the thyroid.

126. Dexamethasone. Dexamethasone, 2 mg every 6 hours, inhibits the peripheral conversion of T4 to T3 and has wellknown immunosuppressive effects.186 The inhibitory effect of dexamethasone on conversion of T4 to T3 is additive to that of propylthiouracil, suggesting a different mechanism of action. Concurrent administration of propylthiouracil, SSKI, and dexamethasone to a patient with severe, lifethreatening thyrotoxicosis effects a rapid reduction in serum T3 concentration, often to the normal range within 24 to 48 hours

127. β-Blocking Agents. Drugs that block the response to catecholamines at the receptor site (e.g., propranolol) ameliorate some of the manifestations of thyrotoxicosis and are often used as adjuncts in management. Tremulousness, palpitations, excessive sweating, eyelid retraction, and heart rate decrease; effects are rapidly manifested and appear to be mediated largely through modulation of the increased sensitivity to the sympathetic nervous system induced by excess thyroid hormone (described earlier).20,22 Propranolol. but not other  -adrenergic blockers, may also weakly block the conversion of T4 to T3 via a mechanism independent of its effect on catecholamine signaling

128. TABLE 12-5 Complications of Surgery in 322 Patients with Graves’ Hyperthyroidism in Experienced Hands (1986-1995) Complication % Recurrent hyperthyroidism 2.0 Vocal cord paralysis Transient 2.5 Permanent 0.3 Prolonged postoperative hypocalcemia (  7 days) 3.7 Permanent hypoparathyroidism 0.6

129. COMPLICATIONS OF RADIOIODINE THERAPY #1—Thyroid Cancer from Low-Level Exposure. There is no increase in thyroid cancer or any other cancer after diagnostic or therapeutic use of radioiodine in hyperthyroid adults,206 in accord with earlier reports.193 However,

130. # 2—Mortality after Radioiodine. Patients treated with radioiodine for hyperthyroidism had increased mortality compared with age- and period-specific mortality rates in the background population.

131. #3—Hypothyroidism after Radioiodine. In theory, the therapeutic goal of 131I administration is to induce euthyroidism so that Graves’ disease cannot recur. However, the incidence of hypothyroidism is significant during the first year or two after treatment with radioiodine, regardless of how the dose is calculated

132. # 4—Radiation Thyroiditis. The early euthyroidism and later hypothyroidism are both consequences of radiation-induced destruction of thyroid parenchyma. With larger doses of radioactive iodine, a tender radiation thyroiditis may develop within the first week after treatment, as evidenced by epithelial swelling and necrosis, disruption of follicular architecture, edema, and infiltration with mononuclear cells

133. # 5—Orbitopathy and Radioiodine. As discussed earlier, Graves’ orbitopathy is probably the result of a cross-over specificity between retroorbital and thyroid antigens, including the TSHR itself. Therefore, any worsening of the autoimmune thyroid response might worsen the orbital immune response. After radioiodine therapy, the levels of circulating TRAbs are strikingly elevated,57,211 perhaps secondary to impairment of immune restraint caused by the intrathyroidal irradiation that renders regulatory cells more sensitive

134. # 6—Other Side Effects of Radioiodine. Additional hazards may attend the use of radioiodine, particularly in large doses. The parathyroid glands are exposed to radiation in patients treated with radioiodine. Although parathyroid reserve may be diminished in some patients, development of overt hypoparathyroidism is rare

135. The effect of radioiodine on other tissues that concentrate iodide (e.g., salivary glands, gastric glands, breasts) has often had attention but is not likely to be a problem with the relatively low doses prescribed for Graves’ disease compared with the treatment of thyroid cancer.

136. TABLE 12-6 Diagnostic Criteria for Thyroid Storm Diagnostic Parameter Points* Temperature (° F) 99-99.9 5 100-100.9 10 101-101.9 15 102-102.9 20 103-103.9 25  104.0 30

137. Central Nervous System Effects Absent 0 Mild (agitation) 10 Moderate (delirium, psychosis, extreme lethargy) 20 Severe (seizures, coma) 30

138. Gastrointestinal-Hepatic Dysfunction Absent 0 Moderate (diarrhea, nausea/vomiting, abdominal pain) 10 Severe (unexplained jaundice) 20

139. Cardiovascular Dysfunction Tachycardia (beats/min) 90-109 5 110-119 10 120-129 15 130-139 20  140 25 Congestive Heart Failure Absent 0 Mild (pedal edema) 5 Moderate (bibasilar rales) 10

140. Precipitating Event Absent 0 Present 10 Severe (pulmonary edema) 15 Atrial Fibrillation Absent 0 Present 10

141. Scoring system: A score of 45 or greater is highly suggestive of thyroid storm; 25-44 is suggestive of impending storm, and  25 is unlikely to represent thyroid storm

142. TABLE 12-9 Indications for Treatment of Persistent Subclinical Hyperthyroidism Postmenopausal osteoporosis Rheumatic valvular disease with left atrial enlargement or atrial fibrillation Recent-onset atrial fibrillation or recurrent cardiac arrhythmias Congestive heart failure

143. trial) Angina pectorisInfertility or menstrual disorders Nonspecific symptoms such as fatigue, nervousness, depression, or gastrointestinal disorders, especially in patients older than 60 years of age (consider therapeu tic

144. Table 8. Subclinical Hyperthyroidism: When to Treat FactorTSH (<0.1 mU/L)TSH (0.1–0.5 mU/L)a Age >65YesConsider treating Age <65 with comorbidities Heart diseaseYesConsider treating OsteoporosisYesNo MenopausalConsider treatingConsider treating Hyperthyroid symptomsYesConsider treating Age <65, asymptomaticConsider treatingNo

145. RECOMMENDATION 52 Pediatric patients and their caretakers should be informed of side effects of antithyroid drugs and the necessity of stopping the medication immediately and informing their physician if they develop pruritic rash, jaundice, acolic stools or dark urine, arthralgias, abdominal pain, nausea, fatigue, fever, or pharyngitis

146. RECOMMENDATION 53 Prior to initiating antithyroid drug therapy, we suggest that pediatric patients have, as a baseline, complete blood cell count, including white blood cell count with differential, and a liver profile including bilirubin, transaminases, and alkaline phosphatase

147. RECOMMENDATION 54 Beta adrenergic blockade is recommended for children experiencing symptoms of hyperthyroidism, especially those with heart rates in excess of 100 beats per minute.

148. RECOMMENDATION 55 Antithyroid medication should be stopped immediately, and white blood counts measured in children who develop fever, arthralgias, mouth sores, pharyngitis, or malaise.

149. RECOMMENDATION 57 Persistent minor cutaneous reactions to methimazole therapy in children should be managed by concurrent antihistamine treatment or cessation of the medication and changing to therapy with radioactive iodine or surgery. In the case of a serious allergic reaction to an antithyroid medication, prescribing the other antithyroid drug is not recommended. 1

150. RECOMMENDATION 58 If methimazole is chosen as the first-line treatment for GD in children, it should be administered for 1–2 years and then discontinued, or the dose reduced, to assess whether the patient is in remission

151. FACTORS THAT MAY IMPACT PATIENT PREFERENCE

152. a. 131I therapy: Patients choosing 131I therapy as treatment for GD would likely place relatively higher value on definitive control of hyperthyroidism, the avoidance of surgery, (

153. and the potential side effects of antithyroid medications, as well as a latively lower value on the need for lifelong thyroid hormone replacement, rapid resolution of hyperthyroidism, and potential worsening or development of GO

154. ATDs: Patients choosing antithyroid drug therapy as treatment for GD would place relatively higher value on the possibility of remission and the avoidance of lifelong thyroid hormone treatment, the avoidance of surgery, and exposure to radioactivity and a relatively lower value on the

155. Surgery: Patients choosing surgery as treatment for GD would likely place a relatively higher value on prompt and definitive control of hyperthyroidism, avoidance of exposure to radioactivity, and the potential side effects of ATDs and a relatively lower value on potential surgical risks and need for lifelong thyroid hormone replacement

156. RECOMMENDATION 31 We suggest that patients with overtly TMNG or TA be treated with either 131I therapy or thyroidectomy. On occasion, long-term, low-dose treatment with methimazole may be appropriate.

157. ■ RECOMMENDATION 38 If hyperthyroidism persists beyond 6 months following 131I therapy for TMNG or TA, retreatment with radioactive iodine is suggested.

158. RECOMMENDATION 37 Follow-up within the first 1–2 months after radioactive iodine therapy for TMNG or TA should include an assessment of free T4, total T3 and TSH. This should be repeated at 1–2 month intervals until stable results are obtained, then at least annually thereafter according to clinical indication.

159. ■ RECOMMENDATION 39 If surgery is chosen as treatment for TMNG or TA, patients with overt hyperthyroidism should be rendered euthyroid prior to the procedure with methimazole pretreatment (in the absence of allergy to the medication), with or without beta-adrenergic blockade. Preoperative iodine should not be used in this setting

160. RECOMMENDATION 40 If surgery is chosen as treatment for TMNG, near- total or total thyroidectomy should be performed

161. RECOMMENDATION 41 Surgery for TMNG should be performed by a high-volume thyroid surgeon.

162. RECOMMENDATION 44 Following thyroidectomy for TMNG, we suggest that serum calcium or intact parathyroid hormone levels be measured, and that oral calcium and calcitriol supplementation be administered based on these results.

163. RECOMMENDATION 45 Methimazole should be stopped at the time of surgery for TMNG or TA. Beta- adrenergic blockade should be slowly discontinued following surgery.

164. RECOMMENDATION 46 Following surgery for TMNG, thyroid hormone replacement should be started at a dose appropriate for the patient’s weight (0.8 mcg/lb or 1.7 mcg/kg) and age, with elderly patients needing somewhat less. TSH should be measured every 1–2 months until stable, and then annually. 1/+00

165. RECOMMENDATION 47 Following surgery for TA, TSH and estimated free T4 levels should be obtained 4–6 weeks after surgery, and thyroid hormone supplementation started if there is a persistent rise in TSH above the normal range. 1/

166. RECOMMENDATION 48 Radioactive iodine therapy should be used for retreatment of persistent or recurrent hyperthyroidism following inadequate surgery for TMNG or TA.

167. RECOMMENDATION 49 We suggest that long-term methimazole treatment of TMNG or TA be avoided, except in some elderly or otherwise ill patients with limited longevity who are able to be monitored regularly, and in patients who prefer this option.

168. …. acceptable if the calculated 131I administered activity is 150 μCi/g of thyroid tissue

169. Thyroidectomy should be chosen when definitive therapy is required, the child is too young for 131I, and surgery can be performed by a high-volume thyroid surgeon

170. Once SH has been detected, it is important to document that it is a persistent problem by repeating the serum TSH at 3 or 6 months. Some reports suggest that a subnormal serum TSH may spontaneously resolve, especially if the levels are >0.05 mU/L (250– 252). Patients with GD rather than a TMNG as the cause of SH may be more likely to spontaneously remit (253).

171. R2] Clinical significance of SH Since SH is a mild form of hyperthyroidism, deleterious effects on the cardiovascular system and the skeleton might be expected in some patients, and subtle symptoms of thyrotoxicosis or altered cognition might also be potential problems.

172. Regarding cardiac complications, one study found a 2.8-fold risk of atrial fibrillation in persons over age 60 years with SH (254), which has been confirmed in another population over age 65 years (255).

173. Postmenopausal women with SH may have increased fracture rates even with only mildly suppressed serum TSH levels (259), as well as improvement in bone mineral density with therapy of SH with antithyroid drugs or radioactive iodine in controlled but nonrandomized intervention studies (260,261).

174. RECOMMENDATION 65 When TSH is persistently <0.1 mU/L, treatment of SH should be strongly considered in all individuals ≥65 years of age, and in postmenopausal women who are not on estrogens or bisphosphonates; patients with cardiac risk factors, heart disease or osteoporosis; and individuals with hyperthyroid symptoms.